Background & Aims: Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP. Methods: In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac alone group, n=442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n=444). The primary endpoint was the occurrence of PEP. Results: Post-ERCP pancreatitis developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac alone group (9.5%) (relative risk, 0.59; 95% CI, 0.37-0.95; P=.03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in 6 the combination group, and 10 patients (2.3%) in the diclofenac alone group (relative risk, 0.12; 95% CI, 0.13-1.26; P = 0.12). There was no serious adverse event related to the additional administration of sublingual nitrate. Conclusions: In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274

AIM:To evaluate the effectiveness of endoscopic submucosal dissection using an insulation-tipped diathermic knife (IT-ESD) for the treatment of patients with gastric remnant cancer. METHODS:Thirty-two patients with early gastric cancer in the remnant stomach, who underwent distal gastrectomy due to gastric carcinoma, were treated with endoscopic mucosal resection (EMR) or ESD at Sumitomo Besshi Hospital and Shikoku Cancer Center in the 10-year period from January 1998 to December 2007, including 17 patients treated with IT-ESD. Retrospectively, patient backgrounds, the one-piece resection rate, complete resection (CR) rate, operation time, bleeding rate, and perforation rate were compared between patients treated with conventional EMR and those treated with IT-ESD. RESULTS:The CR rate (40% in the EMR group vs 82% in the IT-ESD group) was significantly higher in the IT-ESD group than in the EMR group; however, the operation time was significantly longer for the IT-ESD group (57.6 ± 31.9 min vs 21.1 ± 12.2 min).No significant differences were found in the rate of underlying cardiopulmonary disease (IT-ESD group, 12% vs EMR group, 13%), one-piece resection rate (100% vs 73%), bleeding rate (18% vs 6.7%), and perforation rate (0% vs 0%) between the two groups. CONCLUSION:IT-ESD appears to be an effective treatment for gastric remnant cancer post distal gastrectomy because of its high CR rate. It is useful for histological confirmation of successful treatment. The long-term outcome needs to be evaluated in the future.

Summary:We retrospectively compared the incidence of acute graftversus-host disease (GVHD) before and after September 1999, when we changed the mode of cyclosporine A (CsA) administration from twice-daily infusions (TD) (n ¼ 58) to continuous infusion (CIF) (n ¼ 71). The incidence of grade II-IV acute GVHD in the CIF group (56%) was significantly higher than that in the TD group (27%, P ¼ 0.00022). Multivariate analysis identified only two independent significant risk factors for the development of grade II-IV acute GVHD; CIF of CsA (relative risk 2.59, 95% CI 1.46-4.60, P ¼ 0.0011) and the presence of HLA mismatch (2.01, 95% CI 1.15-3.53, P ¼ 0.014). The incidence of relapse was significantly lower in the CIF group when adjusted for disease status before transplantation (0.41, 95% CI 0.18-0.95, P ¼ 0.038), which resulted in better disease-free survival in high-risk patients (43 vs 16% at 2 years, P ¼ 0.039), but not in standard-risk patients (72 vs 80%, P ¼ 0.45). CIF of CsA with a target level of 250-400 ng/ml may not be appropriate for GVHD prophylaxis in standard-risk patients.

We successfully prepared a series of thermally stable polyimides (PIs) with low dielectric constant (k) by introducing bulky diphenyl fluorenylidene moieties in backbone. The lowest k was found to be 2.77 among non‐fluorinated PIs and 2.35 among fluorinated ones. In order to prove the lowest limit of k in PIs, we prepared soluble and thermally stable polyarylenes (PArs) without polar imide linkage with the same aromatic moieties by coupling polymerization. The lowest k was 2.7 without fluorine (F) and 2.2 with F atom, which showed also promising for low k materials. From these results, PIs we prepared were estimated to the lowest k values among PIs. On the basis of statistics on these results, we could express contour lines of k as a function of imide concentration and F content with high correlation factor (r= 0.96) in PIs and PArs.

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelial-mesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low-and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased Ecadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low-and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.